Efinaconazole

Efinaconazole topical solution is an azole antifungal.

The pharmacodynamics of efinaconazole is unknown.

Systemic absorption of efinaconazole in 18 adult subjects with severe onychomycosis was determined after application of efinaconazole once daily for 28 days to patients' 10 toenails and 0.5 cm adjacent skin. The concentration of efinaconazole in plasma was determined at multiple time points over the course of 24-hour periods on Days 1, 14, and 28. Efinaconazole mean ± SD plasma C_max on Day 28 was 0.67 ± 0.37 ng/mL and the mean ± SD AUC was 12.15 ± 6.91 h•ng/mL. The plasma concentration versus time profile at steady state was generally flat over a 24-hour dosing interval. In a separate study of healthy volunteers, the plasma half-life of efinaconazole following daily applications when applied to all 10 toenails for 7 days was 29.9 hours.

Specific Populations

Pediatric patients

PK of efinaconazole was assessed in 17 pediatric subjects 12 to <17 years of age with moderate to severe onychomycosis following application of efinaconazole once daily to all 10 toenails for 28 days.

The plasma concentrations of efinaconazole in pediatric subjects were relatively flat over a 24-hour dosing interval. The mean ± SD plasma C_max and AUC_0-24 for efinaconazole on Day 28 were 0.55±0.38 ng/mL and 11.4±7.68 h•ng/mL, respectively.

Drug Interactions

Efinaconazole is considered a non-inhibitor of the CYP450 enzyme family. In in vitro studies using human liver microsomes, efinaconazole did not inhibit CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2PE1 and CYP3A4 enzyme activities at expected clinical systemic concentrations. In vitro studies in human primary hepatocytes showed that efinaconazole did not induce CYP1A2 or CYP3A4 activities.